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Chapter 27: A Review of Metabolism Copyright 2007 by W. H. Freeman and Company Berg Tymoczko Stryer Biochemistry Sixth Edition Slide 2 Basic Features of Metabolism 1. ATP is the universal currency. Coupling of ATP hydrolysis can produce a favorable G o'. 2. ATP is produced by oxidation of carbohydrate (glucose), fat (fatty acids) and protein (amino acids). AcetylCoA is a central intermediate. 3. NADPH provides reductive power for synthesis and most of it is produced by the HMS. 4. Biomolecules are made from pool molecules. 5. Pathways of catabolism and anabolism are always distinct. This facilitates regulation. Slide 3 Themes in Regulation 1. Allosteric regulation: enzyme activity being modulated by binding of metabolites. Typically at the site of a key regulatory enzyme. 2. Covalent regulation: enzyme activity being modulated by a covalent attachment. 3. Genetic control: Induction or repression of the gene for an enzyme. 4. Cell compartmentation: Some pathways are segregated by occurring in different organelles. 5. Organ specialization: Some pathways occur in different organs. Slide 4 Covalent Regulation PhosphorylationAdenylation Slide 5 Pathways in Different Organelles Slide 6 Regulatory Enzymes & Sites 1. Glycolysis:phosphofructokinase-1 occurs in the cytosol 2. Krebs Cycle:isocitrate dehydrogenase occurs in the mitochondria 3. Pyruvate Dehydrogenase Complex:E1, PDH occurs in the mitochondria 4. Pentose phosphate:glucose-6-P dehydrogenase occurs in the cytosol 5. Gluconeogenesis: fructose-1,6-bisphosphatase occurs in the liver Slide 7 Regulatory Enzymes & Sites 6. Glycogen breakdown: phosphorylase occurs in the cytosol 7. Glycogen synthesis: glycogen synthase occurs in the cytosol 8. Fatty acid anabolism: acetylCoA carboxylase occurs in the cytosol 9. Fatty acid catabolism: carnitineacyl transferase I occurs in the mitochondria Slide 8 Glycolysis Slide 9 Pentose Phosphate (HMS) Inhibited by NADPH and fatty acylCoA Slide 10 Glyconeogenesis Slide 11 Fatty Acid Synthesis Slide 12 -Oxidation Slide 13 Key Junctions 1. Glucose-6-phosphate junction: Traps glucose in a muscle cell and can lead to glucose in a liver cell (gluconeogenesis). Feeds glycolysis to make energy as ATP. Feeds the HMS for NADPH and ribose-5-P. Leads to and from glycogen. 2. Pyruvate junction: End product of glycolysis. Leads to lactate (anaerobic glycolysis). Transamination gives alanine. Slide 14 Key Junctions 2. Pyruvate junction cont.: Leads to oxaloacetate (anaplerotic reaction). Leads to acetylCoA. 3. AcetylCoA junction: Formed from pyruvate, Feeds the Krebs cycle which leads to ET & OP. Leads to and from fatty acids. Leads to ketone bodies. Leads to cholesterol and its derivatives. Slide 15 Glucose-6-P Slide 16 Pyruvate & AcetylCoA Slide 17 End of Chapter 27 Copyright 2007 by W. H. Freeman and Company Berg Tymoczko Stryer Biochemistry Sixth Edition